The yeast gene MSC2, a member of the cation diffusion facilitator family, affects the cellular distribution of zinc

The sequence of the yeast gene YDR205W places it within the family of cation diffusion facilitators: membrane proteins that transport transition metals. Deletion of YDR205W was reported to result in an increase in unequal sister chromatid recombination and was named meiotic sister chromatid recombination 2 (MSC2; Thompson, D. A., and Stahl, F, W. (1999) Genetics 153, 621-641), We report here that a msc2 strain shows a phenotype of decreased viability in glycerol-ethanol media at 37 degreesC, Associated with decreased growth is an abnormal morphology typified by an increase in size of both cells and vacuoles. Addition of extracellular Zn2+ completely suppresses the morphological changes and partially suppresses the growth defect. Regardless of the concentration of Zn2+ in the media, the msc2 strain had a higher Zn2+ content than wild type cells. Zinquin staining also revealed that msc2 had a marked increase in fluorescence compared with the wild type, again reflecting an increase in intracellular Zn2+, The deletion strain accumulated excess Zn2+ in nuclei-enriched membrane fractions, and when grown at 37 degreesC in glycerol-ethanol media, it showed a decreased expression of Zn2+-regulated genes. The expression of genes regulated by either Fe2+ or Cu2+ was not affected. An epitope-tagged Msc2p was localized to the endoplasmic reticulum/nucleus, These results suggest that Msc2p affects the cellular distribution of zinc and, in particular, the zinc content of nuclei.